Annals of Medical and Clinical Amouzoune S, et al. Ann med clin Oncol: AMCO-106. Case Report DOI: 10.29011/AMCO-106.000106 Bilateral Ovarian Malignant Brenner Tumor: A Case Report with Lit- erature Review S. Amouzoune1*, A. Belbachir1, S. Berrada1, C. Ahouissoussi1, Y. Khimari2, K. Harou2, A. Soumani2, H. Rais1 1Department of Anatomy , Mohammed VI University Hospital, Marrakech, Morocco 2Department of Gynecology, Mohammed VI University Hospital, Marrakech, Morocco

*Corresponding author: S. Amouzoune, Department of Anatomy Pathology, Mohammed VI University Hospital, Marrakech, Morocco Email: [email protected] Citation: Amouzoune S, Belbachir A, Berrada S, Ahouissoussi C, Khimari Y, et al. (2019) Bilateral Ovarian Malignant Brenner Tumor: A Case Report with Literature Review. Ann med clin Oncol 2: 106. DOI: 10.29011/AMCO-106.000106 Received Date: 03 December, 2018; Accepted Date: 03 January, 2018; Published Date: 09 January, 2019

Abstract Brenner tumor of the is very rare, mostly benign, small, and unilateral. Malignant Brenner Tumor (MBT) is much rarer. We present a patient aged 50 years, with no specific pathological history who presented in consultation for chronic pelvic pain. Pelvic ultrasound demonstrated a bilateral latero-uterine mass of suspicious appearance with local infiltration with peritoneal carcinosis and an ascites of average abundance. The pathological examination had concluded in a bilateral brenner tumor, endometrium, omentum are all invaded. Brenner tumors are rare ovarian tumors, first described by McNaughton-Jones in 1898 and then named by Frits Brenner in 1907. MBT presents similarly to other ovarian cancers (abdominal distension, abdominal pain, bulk symptoms and relative vague symptomatology). All histopathological diagnoses were performed according to the criteria described by Hull and Campbell. Tumors express several immunohistochemical markers of urothelial differentiation including uroplakin III, thrombomodulin, GATA3, p63, as well as cytokeratin 7. The primary treatment modality is surgical excision. This study discussed the clinical, pathological characteristics and treatment of MBTs.

Introduction Case Report Ovarian Brenner tumors are relatively rare, comprising Patient aged 50 years, with no specific pathological history, 1% to 3% of all ovarian [1]. Brenner tumor of the nulligeste, presented in consultation for chronic pelvic pain, pelvic ovary is a relatively uncommon . The average age at ultrasound had objectified a suspected bilateral presentation is 50 years with 71% of the patients being more than of 5cm / 5cm on each side, with thickened wall and endokytic 40 years [2]. It has a predilection for the postmenopausal woman. vegetations with ascites, vascularized with doppler, abdomino- According to WHO, depending on the histopathological pattern, pelvic CT demonstrated a bilateral latero-uterine mass of suspicious they are classified as benign, borderline or malignant Brenner appearance with local infiltration with peritoneal carcinosis and an tumors, and transitional cell carcinomas [3]. Although Brenner ascites of average abundance. An exploratory laparotomy made, tumors are usually discovered incidentally, patients occasionally which had found an unilateral white-cystic tumor of greyish white present with symptoms such as a palpable mass or pain [4]. appearance, irregular wall adherent to the neighboring structures, They are usually unilateral; bilateral lesions are found in 5-14% infiltrating the right broad ligaments, rectum and douglas sac of cases [4]. Brenner tumor is a fibroepithelial tumor composed with nodules at the omentum And peritoneal carcinosis, a total of transitional epithelial cell nests, similar to bladder epithelium hysterectomy without adnexal preservation with cytological [5]. The conventional treatment modality is surgical resection; sampling and an omentectomy with multiple parietal biopsies however, only a little information is available on the definition, were performed. The pathological examination had concluded in biology, optimal treatment, and prognosis of Malignant Brenner a bilateral malignant brenner tumor, endometrium, omentum are Tumors (MBTs) [6]. all invaded (Figure 1). The Immunohistochemistry staining results

1 Volume 2; Issue 01 Citation: Amouzoune S, Belbachir A, Berrada S, Ahouissoussi C, Khimari Y, et al. (2019) Bilateral Ovarian Malignant Brenner Tumor: A Case Report with Literature Review. Ann med clin Oncol: AMCO-106. DOI: 10.29011/AMCO-106.000106 were positive for: WT-1, cytokeratin 7 and negative for cytokeratin20, and p63 (Figure 2).

Figure 1: (A): Benign Brenner tumor shows solid and cystic nests of bland epithelial cells that resemble a transitional epithelium surrounded by abundant dense fibroblastic stromal tissue. (Hex10;(B): Malignant Brenner tumor component shows a cytologically malignant component with stromal invasion (He x 40).

Figure 2: Immunohistochemical stains were performed to rule out other tumors. Wt1 (A) CK7 (B) are positive. CK20 (C) is negative. Controls were reactive. The results of the stain support the diagnosis of primary ovarian tumor consistent histologically with malignant Brenner tumor. Discussion A recent retrospective analysis showed that the median tumor size for MBT was 10 cm (10); however, tumor sizes vary with some Ovarian neoplasms are a heterogeneous group composed sources suggesting these neoplasms are typically much smaller of tumors showing epithelial, germ cell, and sex cord stromal (< 2 cm) (10). Usually, benign Brenner tumors are unilateral and differentiation. The ovarian Brenner Tumor (BT) represents a rare malignant Brenner tumors are bilateral [4]. Diagnosing Brenner epithelial ovarian neoplasm and accounts for 1-2% of all ovarian tumors with imaging studies is difficult because the tumor’s neoplasms [7] They are rare ovarian tumors, first described by appearance is nonspecific [4]. In general, it has been shown on CT McNaughton-Jones in 1898 and then named by Frits Brenner in imaging to have nonspecific findings, most consistently reported 1907 [6]. In 2013, Kuhn, et al. suggested a fallopian tube origin as a mild-moderate enhancement with evidence of amorphous for Brenner tumors based on morphologically identical cilia on calcification confined to the solid component [11]. Malignant the fallopian tube and ovarian surface, as well as a very similar Brenner tumors are not associated with findings consistent with immunohistochemistry profile in the two tissues [8]. Brenner hemorrhage or necrosis; however, these features, along with a tumors are usually benign tumors, although there is a wide spectrum thick irregular wall, thick septa and papillary projections are between benign and malignant features [4]. MBT presents similarly typical features of malignant epithelial ovarian tumors [7]. to other ovarian cancers (abdominal distension, abdominal pain, bulk symptoms and relative vague symptomatology) [9]. Patients All histopathological diagnoses were performed according typically present with disease confined to the ovary or surrounding to the criteria described by Hull and Campbell [12], which tissue with lymphatic spread being less common [10]. complemented Idelson’s [13] criteria as follows: (a) presence

2 Volume 2; Issue 01 Citation: Amouzoune S, Belbachir A, Berrada S, Ahouissoussi C, Khimari Y, et al. (2019) Bilateral Ovarian Malignant Brenner Tumor: A Case Report with Literature Review. Ann med clin Oncol: AMCO-106. DOI: 10.29011/AMCO-106.000106 of malignant histological features; (b) presence of an intimate residue, it should be noted that in 80% of the cases discovered are association between malignant and benign components or a good prognosis seen the early diagnosis in stage I. borderline Brenner tumor (in the absence of a benign or borderline Brenner component, the tumor should be classified as a transitional Conclusion cell The malignant Brenner tumor is an extremely rare Carcinoma; (c) absence of mucinous cystadenomas or diagnosis of fortuitous discovery, the prognosis of which remains separation of the mucinous cystadenomas from both the benign reserved given the late detection. In the absence of a therapeutic tumor and the MBT; and (d) demonstration of stromal invasion by standard, management is essentially surgical. The indication of epithelial elements of the MBT [6]. The brenner tumor cells have chemotherapy remains questionable and rests on a poly adjuvant hyperchromatic, pleomorphic nuclei and numerous mitotic figures, chemotherapy, several protocols remain uncommitted due to the and they are characterized by destructive stromal invasion [4]. very low incidence of this malignant form, unlike the benign forms Furthermore, associated tumor types (most commonly mucinous of which the therapeutic arsenal is well codified and the prognosis cystadenoma) must either be absent or geographically distinct generally remains very Good. from the MBT [12]. Immunohistochemical stains were performed References to rule out other tumors. CA125, CK7 and WT-1 are positif [7]. The primary tumor on the differential diagnosis of MBT is 1. Tafe LJ, Muller KE, Ananda G, et al. (2016) Molecular Genetic Analysis Transitional cell carcinoma. Despite their shared transitional cell of Ovarian Brenner Tumors and Associated Mucinous Epithelial Neo- plasms; The American Journal of Pathology 186: 3. phenotype, there is considerable evidence that these two tumors represent distinct pathologic and clinical entities. On imaging and 2. Jodha BS, Garg R (2017) Brenner tumor of ovary: an incidental find- gross examination, TCC lacks the calcifications typically seen in ing: a case report; International Journal of Reproduction, Contracep- tion, Obstetrics and Gynecology Jodha BS et al. Int J Reprod Contra- MBT [7]. The TCC is characterized by the presence of nuclei with cept Obstet Gynecol 6: 1132-1135. distinct nuclear grooves (so-called “coffee-bean” shapes) and can be aided with immunohistochemical demonstration of urothelial 3. Gilks CB, Carinelli SG, Liu A, Prat J, Seidman JD, et al. (2014) Brenner tumors. Edited by Kurman RJ, Carcangiu ML, Herrington CS, Young marker expression (such as GATA3, uroplakin III, thrombomodulin, RH, (Eds.): WHO Classification of Tumours of Female Reproductive and p63) [14]. There is one report on the retroperitoneal metastatic Organs. Lyon, IARC 2014. spread of MBT, which was initially limited to the unilateral ovary 4. Turgay B, Koyuncu K, Taşkın S, Ortaç UF (2017) Features of ovarian without regional or distant metastasis [6]. Thus, a biopsy of Brenner tumors: Experience of a single tertiary center; Turk J Obstet pelvic lymph nodes should be recommended, even if the tumor is Gynecol 14: 133-137. localized only to the unilateral ovary without metastasis. Unilateral 5. Vranes HS, Klaric P, Benkovik LB, Pirkic A (2005) Brenner tumor of the oophorectomy is the procedure of choice only for benign Brenner ovary. Acta Clin Croat 44: 271-273. tumors in patients who desire ovarian conservation [6]. Ben Aissia, 6. Han JH, Kim D, Lee S, Kim YT, Nam JH et al. (2015) Intensive sys- et al. reported that metastasis occurs in half of the cases and are temic chemotherapy is effective against recurrent malignant Brenner mostly locoregional [15]. tumor of the ovary: An analysis of 10 cases within a single cente ; Taiwanese Journal of Obstetrics & Gynecology 54: 178-182. The treatment for Brenner tumor is essentially surgical. Surgical staging should be done if a tumor has malignant potential. 7. Lang SM, Mills AM, Cantrell LA (2017) Malignant Brenner tumor of The role of lymphadenectomy is not yet clear because of the rare the ovary: Review and case report; Reports 22: 26-31. occurence of malignant Brenner tumors. It is reported that the rate of lymph node metastasis was 5.1% and lymphadenectomy was 8. Kuhn E, Ayhan A, Shih Ie M, Seidman JD, Kurman RJ (2013) Ovar- not associated with any improvement in survival [10], and Han, ian Brenner tumour: a morphologic and immunohistochemical analysis suggesting an origin from fallopian tube epithelium. 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(2012) CT and MR imaging Brenner tumors of advanced stages are poor prognosis with an of ovarian tumors with emphasis on differential diagnosis. Radiograph- average survival at 5 years not exceeding 40% [17]. The factors of ics 22: 1305-1325. poor prognosis associates, Young age, advanced stage and tumor

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12. Hull MG, Campbell GR (1973) The malignant Brenner tumor. Obstet 15. Aissia NB, Sadfi A, Youssef A, El Ayeb A, Chadli A, et al. (2004) Malign Gynecol 42: 527e34. Brenner’s tumor particularities and coverage. Tunis Med 82: 701-707.

13. Idelson MG (1963) Malignancy in Brenner tumors of the ovary, with 16. Przybycin CG, Soslow RA (2011) Typing of ovarian carcinomas: an comments on histogenesis and possible estrogen production. Obstet update. Diagnostic Histopathology 17: 165-177. Gynecol Surv 18: 246-267. 17. Van Der Weiden RMF, Gratama S (1987) Proliferative and malignant 14. Roma AA, Masand RP (2015) Different staining patterns of ovar- Brenner tumours (BT) and their differentiation from metastatic transi- ian Brenner tumor and the associated mucinous tumor. Ann. Diagn. tional cell carcinoma of the bladder: a case report and review of the Pathol 19: 29-32. literature. Eur J Obstet Gynecol Reprod Biol 26: 251-260.

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